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| http://dx.doi.org/10.1016/j.immuni.2019.09.019 | DOI Listing |
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Long lived liver-resident memory T cells of biased specificities for abundant sporozoite antigens drive malaria protection by radiation-attenuated sporozoite vaccination.
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Department of Microbiology and Immunology, The Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, Victoria, Australia.
Vaccination with radiation-attenuated sporozoites (RAS) can provide highly effective protection against malaria in both humans and mice. To extend understanding of malaria immunity and inform the development of future vaccines, we studied the protective response elicited by this vaccine in C57BL/6 mice. We reveal that successive doses of Plasmodium berghei RAS favour the generation of liver CD8+ tissue-resident memory T cells (TRM cells) over circulating memory cells and markedly enhance their longevity.
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Department of Microbiology and Immunology, The Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, VIC 3000, Australia. Electronic address:
We recently demonstrated that vaccines comprising antigenic peptides conjugated to a glycolipid agonist, termed glycolipid-peptide (GLP) vaccines, efficiently generate substantial numbers of long-lived CD8 liver-resident memory T (Trm) cells that are crucial for protection against malaria liver-stage infection. To understand the underlying mechanism, we examined the prerequisites for priming, differentiation, and secondary boosting of liver Trm cells using these GLP vaccines. Our study revealed that generation of long-lived liver Trm cells relies on CD8 T cell priming by type 1 conventional dendritic (cDC1) cells, followed by post-priming exposure to a combination of vaccine-derived inflammatory and antigenic signals.
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Tissue-resident lymphocytes (TRLs) provide a front-line immunological defense mechanism uniquely placed to detect perturbations in tissue homeostasis. The heterogeneous TRL population spans the innate to adaptive immune continuum, with roles during normal physiology in homeostatic maintenance, tissue repair, pathogen detection, and rapid mounting of immune responses. TRLs are especially enriched in the liver, with every TRL subset represented, including liver-resident natural killer cells; tissue-resident memory B cells; conventional tissue-resident memory CD8, CD4, and regulatory T cells; and unconventional gamma-delta, natural killer, and mucosal-associated invariant T cells.
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Laboratory of Precision Medicine and Cancer Evolution, Genome Institute of Singapore, Agency for Science, Technology and Research (A∗STAR), 60 Biopolis St., #02-01 Genome, Singapore 138672. Electronic address:
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